Opicapone Improves the Pharmacokinetics of Levodopa Administered as Extended-Release Capsules

Both a catechol-O-methyltransferase inhibitor and extended-release (ER) levodopa formulations may enhance levodopa treatment through a more continuous levodopa delivery to the striatum; the combination of these therapies has not undergone a pharmacokinetic study. We evaluated the effects of once-daily opicapone 50 mg on levodopa plasma pharmacokinetics when added to a carbidopa/levodopa (CD/LD)-ER formulation (RYTARY®).

This was an exploratory, open-label study of levodopa's pharmacokinetics measured over 24 hours in healthy adults. Enrolled individuals received CD/LD-ER three times daily (TID) alone for 3 days, followed by once-daily opicapone for 14 days. On the last 3 days of the opicapone regimen, participants received CD/LD ER TID again. Pharmacokinetic parameters were evaluated after the 3-day exposure to CD/LD-ER alone and with concomitant administration of opicapone.

Eighteen healthy adults (9 male, 9 female) entered and completed the study. Levodopa exposure (area under the time-concentration curve) was higher with opicapone than with CD/LD-ER alone across all dosing intervals, including between 21:00 and 07:00 (10801.5 vs. 5153.3 ng/mL·h). Over 24 hours, mean levodopa trough concentration (Ctrough) was higher with opicapone versus CD/LD-ER alone (677.2 vs. 266.8 ng/mL), as was minimum Ctrough (302.9 vs. 41.3 ng/mL). There was a greater increase in Ctrough (208%) than in maximum plasma concentration (75%), decreasing the fluctuation index by 38%.

Adding opicapone to CD/LD-ER enhanced levodopa pharmacokinetics in healthy adults, by increasing levodopa trough levels. Notably, opicapone increased overnight and morning levodopa concentrations and decreased daily levodopa concentrations, sub-therapeutic for Parkinson disease patients.